Mercaptopurine (6-MP) — Drug Monograph

Brand names: Purinethol, Purixan

Drug class: Antimetabolite

Mechanism of Action

A purine analog (thiopurine) prodrug. Converted intracellularly by HGPRT to thioguanine nucleotides (TGNs), which incorporate into DNA and RNA and inhibit de novo purine synthesis. This disrupts nucleic acid synthesis and is cytotoxic to rapidly dividing leukemic cells. Competing catabolic pathways involve xanthine oxidase (blocked by allopurinol) and thiopurine S-methyltransferase (TPMT); NUDT15 also detoxifies thiopurine nucleotides.

FDA Indications

• Acute lymphoblastic leukemia (ALL) — as part of combination maintenance therapy

Common Side Effects

• Myelosuppression
• Nausea
• Vomiting
• Anorexia
• Diarrhea
• Stomatitis
• Elevated liver enzymes
• Rash

Clinical Pearl

Always screen the med list for allopurinol before dosing 6-MP — the combination can cause life-threatening myelosuppression unless the 6-MP dose is cut to ~25–33%. Patients with TPMT or NUDT15 deficiency (more common in East Asian and Hispanic populations for NUDT15) accumulate excess thioguanine nucleotides and can develop severe, prolonged cytopenias at standard doses; genotype-guided dosing prevents this.

Related Therapies & Mechanisms

• 5-Fluorouracil (5-FU) (Adrucil) — Antimetabolite
• Azacitidine (Vidaza) — Antimetabolite
• Capecitabine (Xeloda) — Antimetabolite
• Cladribine (Leustatin) — Antimetabolite